Joint Testing of Genotypic and Gene-Environment Interaction Identified Novel Association for BMP4 with Non-Syndromic CL/P in an Asian Population Using Data from an International Cleft Consortium
Non-syndromic cleft lip with or without cleft palate (NSCL/P) is a common disorder with complex etiology. The Bone Morphogenetic Protein 4 gene (BMP4) has been considered a prime candidate gene with evidence accumulated from animal experimental studies, human linkage studies, as well as candidate ge...
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| Published in | PloS one Vol. 9; no. 10; p. e109038 |
|---|---|
| Main Authors | , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
Public Library of Science
10.10.2014
Public Library of Science (PLoS) |
| Subjects | |
| Online Access | Get full text |
| ISSN | 1932-6203 1932-6203 |
| DOI | 10.1371/journal.pone.0109038 |
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| Abstract | Non-syndromic cleft lip with or without cleft palate (NSCL/P) is a common disorder with complex etiology. The Bone Morphogenetic Protein 4 gene (BMP4) has been considered a prime candidate gene with evidence accumulated from animal experimental studies, human linkage studies, as well as candidate gene association studies. The aim of the current study is to test for linkage and association between BMP4 and NSCL/P that could be missed in genome-wide association studies (GWAS) when genotypic (G) main effects alone were considered.
We performed the analysis considering G and interactions with multiple maternal environmental exposures using additive conditional logistic regression models in 895 Asian and 681 European complete NSCL/P trios. Single nucleotide polymorphisms (SNPs) that passed the quality control criteria among 122 genotyped and 25 imputed single nucleotide variants in and around the gene were used in analysis. Selected maternal environmental exposures during 3 months prior to and through the first trimester of pregnancy included any personal tobacco smoking, any environmental tobacco smoke in home, work place or any nearby places, any alcohol consumption and any use of multivitamin supplements. A novel significant association held for rs7156227 among Asian NSCL/P and non-syndromic cleft lip and palate (NSCLP) trios after Bonferroni correction which was not seen when G main effects alone were considered in either allelic or genotypic transmission disequilibrium tests. Odds ratios for carrying one copy of the minor allele without maternal exposure to any of the four environmental exposures were 0.58 (95%CI = 0.44, 0.75) and 0.54 (95%CI = 0.40, 0.73) for Asian NSCL/P and NSCLP trios, respectively. The Bonferroni P values corrected for the total number of 117 tested SNPs were 0.0051 (asymptotic P = 4.39*10(-5)) and 0.0065 (asymptotic P = 5.54*10(-5)), accordingly. In European trios, no significant association was seen for any SNPs after Bonferroni corrections for the total number of 120 tested SNPs.
Our findings add evidence from GWAS to support the role of BMP4 in susceptibility to NSCL/P originally identified in linkage and candidate gene association studies. |
|---|---|
| AbstractList | Background Non-syndromic cleft lip with or without cleft palate (NSCL/P) is a common disorder with complex etiology. The Bone Morphogenetic Protein 4 gene (BMP4) has been considered a prime candidate gene with evidence accumulated from animal experimental studies, human linkage studies, as well as candidate gene association studies. The aim of the current study is to test for linkage and association between BMP4 and NSCL/P that could be missed in genome-wide association studies (GWAS) when genotypic (G) main effects alone were considered. Methodology/Principal Findings We performed the analysis considering G and interactions with multiple maternal environmental exposures using additive conditional logistic regression models in 895 Asian and 681 European complete NSCL/P trios. Single nucleotide polymorphisms (SNPs) that passed the quality control criteria among 122 genotyped and 25 imputed single nucleotide variants in and around the gene were used in analysis. Selected maternal environmental exposures during 3 months prior to and through the first trimester of pregnancy included any personal tobacco smoking, any environmental tobacco smoke in home, work place or any nearby places, any alcohol consumption and any use of multivitamin supplements. A novel significant association held for rs7156227 among Asian NSCL/P and non-syndromic cleft lip and palate (NSCLP) trios after Bonferroni correction which was not seen when G main effects alone were considered in either allelic or genotypic transmission disequilibrium tests. Odds ratios for carrying one copy of the minor allele without maternal exposure to any of the four environmental exposures were 0.58 (95%CI = 0.44, 0.75) and 0.54 (95%CI = 0.40, 0.73) for Asian NSCL/P and NSCLP trios, respectively. The Bonferroni P values corrected for the total number of 117 tested SNPs were 0.0051 (asymptotic P = 4.39*10.sup.-5) and 0.0065 (asymptotic P = 5.54*10.sup.-5 ), accordingly. In European trios, no significant association was seen for any SNPs after Bonferroni corrections for the total number of 120 tested SNPs. Conclusions/Significance Our findings add evidence from GWAS to support the role of BMP4 in susceptibility to NSCL/P originally identified in linkage and candidate gene association studies. Non-syndromic cleft lip with or without cleft palate (NSCL/P) is a common disorder with complex etiology. The Bone Morphogenetic Protein 4 gene (BMP4) has been considered a prime candidate gene with evidence accumulated from animal experimental studies, human linkage studies, as well as candidate gene association studies. The aim of the current study is to test for linkage and association between BMP4 and NSCL/P that could be missed in genome-wide association studies (GWAS) when genotypic (G) main effects alone were considered. We performed the analysis considering G and interactions with multiple maternal environmental exposures using additive conditional logistic regression models in 895 Asian and 681 European complete NSCL/P trios. Single nucleotide polymorphisms (SNPs) that passed the quality control criteria among 122 genotyped and 25 imputed single nucleotide variants in and around the gene were used in analysis. Selected maternal environmental exposures during 3 months prior to and through the first trimester of pregnancy included any personal tobacco smoking, any environmental tobacco smoke in home, work place or any nearby places, any alcohol consumption and any use of multivitamin supplements. A novel significant association held for rs7156227 among Asian NSCL/P and non-syndromic cleft lip and palate (NSCLP) trios after Bonferroni correction which was not seen when G main effects alone were considered in either allelic or genotypic transmission disequilibrium tests. Odds ratios for carrying one copy of the minor allele without maternal exposure to any of the four environmental exposures were 0.58 (95%CI = 0.44, 0.75) and 0.54 (95%CI = 0.40, 0.73) for Asian NSCL/P and NSCLP trios, respectively. The Bonferroni P values corrected for the total number of 117 tested SNPs were 0.0051 (asymptotic P = 4.39*10(-5)) and 0.0065 (asymptotic P = 5.54*10(-5)), accordingly. In European trios, no significant association was seen for any SNPs after Bonferroni corrections for the total number of 120 tested SNPs. Our findings add evidence from GWAS to support the role of BMP4 in susceptibility to NSCL/P originally identified in linkage and candidate gene association studies. Non-syndromic cleft lip with or without cleft palate (NSCL/P) is a common disorder with complex etiology. The Bone Morphogenetic Protein 4 gene (BMP4) has been considered a prime candidate gene with evidence accumulated from animal experimental studies, human linkage studies, as well as candidate gene association studies. The aim of the current study is to test for linkage and association between BMP4 and NSCL/P that could be missed in genome-wide association studies (GWAS) when genotypic (G) main effects alone were considered. We performed the analysis considering G and interactions with multiple maternal environmental exposures using additive conditional logistic regression models in 895 Asian and 681 European complete NSCL/P trios. Single nucleotide polymorphisms (SNPs) that passed the quality control criteria among 122 genotyped and 25 imputed single nucleotide variants in and around the gene were used in analysis. Selected maternal environmental exposures during 3 months prior to and through the first trimester of pregnancy included any personal tobacco smoking, any environmental tobacco smoke in home, work place or any nearby places, any alcohol consumption and any use of multivitamin supplements. A novel significant association held for rs7156227 among Asian NSCL/P and non-syndromic cleft lip and palate (NSCLP) trios after Bonferroni correction which was not seen when G main effects alone were considered in either allelic or genotypic transmission disequilibrium tests. Odds ratios for carrying one copy of the minor allele without maternal exposure to any of the four environmental exposures were 0.58 (95%CI = 0.44, 0.75) and 0.54 (95%CI = 0.40, 0.73) for Asian NSCL/P and NSCLP trios, respectively. The Bonferroni P values corrected for the total number of 117 tested SNPs were 0.0051 (asymptotic P = 4.39*10.sup.-5) and 0.0065 (asymptotic P = 5.54*10.sup.-5 ), accordingly. In European trios, no significant association was seen for any SNPs after Bonferroni corrections for the total number of 120 tested SNPs. Our findings add evidence from GWAS to support the role of BMP4 in susceptibility to NSCL/P originally identified in linkage and candidate gene association studies. Background Non-syndromic cleft lip with or without cleft palate (NSCL/P) is a common disorder with complex etiology. The Bone Morphogenetic Protein 4 gene (BMP4) has been considered a prime candidate gene with evidence accumulated from animal experimental studies, human linkage studies, as well as candidate gene association studies. The aim of the current study is to test for linkage and association between BMP4 and NSCL/P that could be missed in genome-wide association studies (GWAS) when genotypic (G) main effects alone were considered. Methodology/Principal Findings We performed the analysis considering G and interactions with multiple maternal environmental exposures using additive conditional logistic regression models in 895 Asian and 681 European complete NSCL/P trios. Single nucleotide polymorphisms (SNPs) that passed the quality control criteria among 122 genotyped and 25 imputed single nucleotide variants in and around the gene were used in analysis. Selected maternal environmental exposures during 3 months prior to and through the first trimester of pregnancy included any personal tobacco smoking, any environmental tobacco smoke in home, work place or any nearby places, any alcohol consumption and any use of multivitamin supplements. A novel significant association held for rs7156227 among Asian NSCL/P and non-syndromic cleft lip and palate (NSCLP) trios after Bonferroni correction which was not seen when G main effects alone were considered in either allelic or genotypic transmission disequilibrium tests. Odds ratios for carrying one copy of the minor allele without maternal exposure to any of the four environmental exposures were 0.58 (95%CI = 0.44, 0.75) and 0.54 (95%CI = 0.40, 0.73) for Asian NSCL/P and NSCLP trios, respectively. The Bonferroni P values corrected for the total number of 117 tested SNPs were 0.0051 (asymptotic P = 4.39*10−5) and 0.0065 (asymptotic P = 5.54*10−5), accordingly. In European trios, no significant association was seen for any SNPs after Bonferroni corrections for the total number of 120 tested SNPs. Conclusions/Significance Our findings add evidence from GWAS to support the role of BMP4 in susceptibility to NSCL/P originally identified in linkage and candidate gene association studies. Non-syndromic cleft lip with or without cleft palate (NSCL/P) is a common disorder with complex etiology. The Bone Morphogenetic Protein 4 gene (BMP4) has been considered a prime candidate gene with evidence accumulated from animal experimental studies, human linkage studies, as well as candidate gene association studies. The aim of the current study is to test for linkage and association between BMP4 and NSCL/P that could be missed in genome-wide association studies (GWAS) when genotypic (G) main effects alone were considered.BACKGROUNDNon-syndromic cleft lip with or without cleft palate (NSCL/P) is a common disorder with complex etiology. The Bone Morphogenetic Protein 4 gene (BMP4) has been considered a prime candidate gene with evidence accumulated from animal experimental studies, human linkage studies, as well as candidate gene association studies. The aim of the current study is to test for linkage and association between BMP4 and NSCL/P that could be missed in genome-wide association studies (GWAS) when genotypic (G) main effects alone were considered.We performed the analysis considering G and interactions with multiple maternal environmental exposures using additive conditional logistic regression models in 895 Asian and 681 European complete NSCL/P trios. Single nucleotide polymorphisms (SNPs) that passed the quality control criteria among 122 genotyped and 25 imputed single nucleotide variants in and around the gene were used in analysis. Selected maternal environmental exposures during 3 months prior to and through the first trimester of pregnancy included any personal tobacco smoking, any environmental tobacco smoke in home, work place or any nearby places, any alcohol consumption and any use of multivitamin supplements. A novel significant association held for rs7156227 among Asian NSCL/P and non-syndromic cleft lip and palate (NSCLP) trios after Bonferroni correction which was not seen when G main effects alone were considered in either allelic or genotypic transmission disequilibrium tests. Odds ratios for carrying one copy of the minor allele without maternal exposure to any of the four environmental exposures were 0.58 (95%CI = 0.44, 0.75) and 0.54 (95%CI = 0.40, 0.73) for Asian NSCL/P and NSCLP trios, respectively. The Bonferroni P values corrected for the total number of 117 tested SNPs were 0.0051 (asymptotic P = 4.39*10(-5)) and 0.0065 (asymptotic P = 5.54*10(-5)), accordingly. In European trios, no significant association was seen for any SNPs after Bonferroni corrections for the total number of 120 tested SNPs.METHODOLOGY/PRINCIPAL FINDINGSWe performed the analysis considering G and interactions with multiple maternal environmental exposures using additive conditional logistic regression models in 895 Asian and 681 European complete NSCL/P trios. Single nucleotide polymorphisms (SNPs) that passed the quality control criteria among 122 genotyped and 25 imputed single nucleotide variants in and around the gene were used in analysis. Selected maternal environmental exposures during 3 months prior to and through the first trimester of pregnancy included any personal tobacco smoking, any environmental tobacco smoke in home, work place or any nearby places, any alcohol consumption and any use of multivitamin supplements. A novel significant association held for rs7156227 among Asian NSCL/P and non-syndromic cleft lip and palate (NSCLP) trios after Bonferroni correction which was not seen when G main effects alone were considered in either allelic or genotypic transmission disequilibrium tests. Odds ratios for carrying one copy of the minor allele without maternal exposure to any of the four environmental exposures were 0.58 (95%CI = 0.44, 0.75) and 0.54 (95%CI = 0.40, 0.73) for Asian NSCL/P and NSCLP trios, respectively. The Bonferroni P values corrected for the total number of 117 tested SNPs were 0.0051 (asymptotic P = 4.39*10(-5)) and 0.0065 (asymptotic P = 5.54*10(-5)), accordingly. In European trios, no significant association was seen for any SNPs after Bonferroni corrections for the total number of 120 tested SNPs.Our findings add evidence from GWAS to support the role of BMP4 in susceptibility to NSCL/P originally identified in linkage and candidate gene association studies.CONCLUSIONS/SIGNIFICANCEOur findings add evidence from GWAS to support the role of BMP4 in susceptibility to NSCL/P originally identified in linkage and candidate gene association studies. Background Non-syndromic cleft lip with or without cleft palate (NSCL/P) is a common disorder with complex etiology. The Bone Morphogenetic Protein 4 gene ( BMP4 ) has been considered a prime candidate gene with evidence accumulated from animal experimental studies, human linkage studies, as well as candidate gene association studies. The aim of the current study is to test for linkage and association between BMP4 and NSCL/P that could be missed in genome-wide association studies (GWAS) when genotypic (G) main effects alone were considered. Methodology/Principal Findings We performed the analysis considering G and interactions with multiple maternal environmental exposures using additive conditional logistic regression models in 895 Asian and 681 European complete NSCL/P trios. Single nucleotide polymorphisms (SNPs) that passed the quality control criteria among 122 genotyped and 25 imputed single nucleotide variants in and around the gene were used in analysis. Selected maternal environmental exposures during 3 months prior to and through the first trimester of pregnancy included any personal tobacco smoking, any environmental tobacco smoke in home, work place or any nearby places, any alcohol consumption and any use of multivitamin supplements. A novel significant association held for rs7156227 among Asian NSCL/P and non-syndromic cleft lip and palate (NSCLP) trios after Bonferroni correction which was not seen when G main effects alone were considered in either allelic or genotypic transmission disequilibrium tests. Odds ratios for carrying one copy of the minor allele without maternal exposure to any of the four environmental exposures were 0.58 (95%CI = 0.44, 0.75) and 0.54 (95%CI = 0.40, 0.73) for Asian NSCL/P and NSCLP trios, respectively. The Bonferroni P values corrected for the total number of 117 tested SNPs were 0.0051 (asymptotic P = 4.39*10 −5 ) and 0.0065 (asymptotic P = 5.54*10 −5 ), accordingly. In European trios, no significant association was seen for any SNPs after Bonferroni corrections for the total number of 120 tested SNPs. Conclusions/Significance Our findings add evidence from GWAS to support the role of BMP4 in susceptibility to NSCL/P originally identified in linkage and candidate gene association studies. Non-syndromic cleft lip with or without cleft palate (NSCL/P) is a common disorder with complex etiology. The Bone Morphogenetic Protein 4 gene (BMP4) has been considered a prime candidate gene with evidence accumulated from animal experimental studies, human linkage studies, as well as candidate gene association studies. The aim of the current study is to test for linkage and association between BMP4 and NSCL/P that could be missed in genome-wide association studies (GWAS) when genotypic (G) main effects alone were considered.We performed the analysis considering G and interactions with multiple maternal environmental exposures using additive conditional logistic regression models in 895 Asian and 681 European complete NSCL/P trios. Single nucleotide polymorphisms (SNPs) that passed the quality control criteria among 122 genotyped and 25 imputed single nucleotide variants in and around the gene were used in analysis. Selected maternal environmental exposures during 3 months prior to and through the first trimester of pregnancy included any personal tobacco smoking, any environmental tobacco smoke in home, work place or any nearby places, any alcohol consumption and any use of multivitamin supplements. A novel significant association held for rs7156227 among Asian NSCL/P and non-syndromic cleft lip and palate (NSCLP) trios after Bonferroni correction which was not seen when G main effects alone were considered in either allelic or genotypic transmission disequilibrium tests. Odds ratios for carrying one copy of the minor allele without maternal exposure to any of the four environmental exposures were 0.58 (95%CI = 0.44, 0.75) and 0.54 (95%CI = 0.40, 0.73) for Asian NSCL/P and NSCLP trios, respectively. The Bonferroni P values corrected for the total number of 117 tested SNPs were 0.0051 (asymptotic P = 4.39*10(-5)) and 0.0065 (asymptotic P = 5.54*10(-5)), accordingly. In European trios, no significant association was seen for any SNPs after Bonferroni corrections for the total number of 120 tested SNPs.Our findings add evidence from GWAS to support the role of BMP4 in susceptibility to NSCL/P originally identified in linkage and candidate gene association studies. |
| Audience | Academic |
| Author | Jabs, Ethylin Wang Yeow, Vincent Schwender, Holger Hetmanski, Jacqueline B. Parker, Margaret M. Zhang, Tianxiao Scott, Alan F. Chen, Qianqian Chong, Samuel S. Chou, Yah-Huei Wu Ye, Xiaoqian Wang, Hong Beaty, Terri H. Zhang, Bo |
| AuthorAffiliation | 6 Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York City, New York, United States of America University of Colorado, United States of America 3 Division of Biology and Biomedical Sciences, Washington University, St. Louis, Missouri, United States of America 8 Department of Pediatrics, National University of Singapore, Singapore, Singapore 1 Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China; Ministry of Health Key Laboratory of Reproductive Health, Beijing, China 4 Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America 7 Department of Plastic Surgery, K K Women's and Children's Hospital, Singapore, Singapore 9 Department of Engineering, Xi'an JiaoTong University, Xi'an, China 10 Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America; Department of Genetics and Genomic Sciences, |
| AuthorAffiliation_xml | – name: 7 Department of Plastic Surgery, K K Women's and Children's Hospital, Singapore, Singapore – name: 9 Department of Engineering, Xi'an JiaoTong University, Xi'an, China – name: 6 Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York City, New York, United States of America – name: 3 Division of Biology and Biomedical Sciences, Washington University, St. Louis, Missouri, United States of America – name: 4 Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America – name: 5 Department of Medical Research, Chang Gung Memorial Hospital, Taipei, Taiwan – name: 11 Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America – name: 1 Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China; Ministry of Health Key Laboratory of Reproductive Health, Beijing, China – name: 2 Mathematical Institute, Heinrich Heine University Duesseldorf, Duesseldorf, Germany – name: 8 Department of Pediatrics, National University of Singapore, Singapore, Singapore – name: University of Colorado, United States of America – name: 10 Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America; Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York City, New York, United States of America |
| Author_xml | – sequence: 1 givenname: Qianqian surname: Chen fullname: Chen, Qianqian – sequence: 2 givenname: Hong surname: Wang fullname: Wang, Hong – sequence: 3 givenname: Holger surname: Schwender fullname: Schwender, Holger – sequence: 4 givenname: Tianxiao surname: Zhang fullname: Zhang, Tianxiao – sequence: 5 givenname: Jacqueline B. surname: Hetmanski fullname: Hetmanski, Jacqueline B. – sequence: 6 givenname: Yah-Huei Wu surname: Chou fullname: Chou, Yah-Huei Wu – sequence: 7 givenname: Xiaoqian surname: Ye fullname: Ye, Xiaoqian – sequence: 8 givenname: Vincent surname: Yeow fullname: Yeow, Vincent – sequence: 9 givenname: Samuel S. surname: Chong fullname: Chong, Samuel S. – sequence: 10 givenname: Bo surname: Zhang fullname: Zhang, Bo – sequence: 11 givenname: Ethylin Wang surname: Jabs fullname: Jabs, Ethylin Wang – sequence: 12 givenname: Margaret M. surname: Parker fullname: Parker, Margaret M. – sequence: 13 givenname: Alan F. surname: Scott fullname: Scott, Alan F. – sequence: 14 givenname: Terri H. surname: Beaty fullname: Beaty, Terri H. |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/25303326$$D View this record in MEDLINE/PubMed |
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| ContentType | Journal Article |
| Copyright | COPYRIGHT 2014 Public Library of Science 2014 Chen et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. 2014 Chen et al 2014 Chen et al |
| Copyright_xml | – notice: COPYRIGHT 2014 Public Library of Science – notice: 2014 Chen et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. – notice: 2014 Chen et al 2014 Chen et al |
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| DOI | 10.1371/journal.pone.0109038 |
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| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 Conceived and designed the experiments: HW QC EWJ AFS THB. Performed the experiments: SSC AFS. Analyzed the data: QC HW JBH HS TZ MP BZ. Wrote the paper: QC HW TZ EWJ AFS THB MP. Subject recruitment and/or diagnosis: Y-HWC SSC VY HS XY HW EWJ AFS THB JBH. Competing Interests: The authors have declared that no competing interests exist. |
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| Snippet | Non-syndromic cleft lip with or without cleft palate (NSCL/P) is a common disorder with complex etiology. The Bone Morphogenetic Protein 4 gene (BMP4) has been... Background Non-syndromic cleft lip with or without cleft palate (NSCL/P) is a common disorder with complex etiology. The Bone Morphogenetic Protein 4 gene... Background Non-syndromic cleft lip with or without cleft palate (NSCL/P) is a common disorder with complex etiology. The Bone Morphogenetic Protein 4 gene (... |
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| SubjectTerms | Alcohol Alcohol use Alcohols Analysis Animal research Asian Continental Ancestry Group - genetics Biology and Life Sciences Bone morphogenetic protein 4 Bone Morphogenetic Protein 4 - genetics Bone morphogenetic proteins Cleft Lip - complications Cleft Lip - etiology Cleft Lip - genetics Cleft lip/palate Cleft Palate - complications Cleft Palate - etiology Cleft Palate - genetics Consent Consortia Epidemiology Ethics Etiology Exposure Female Gene-Environment Interaction Genes Genetic Linkage Genetic Predisposition to Disease Genome-Wide Association Study Genomes Genomics Genotype Genotype-environment interactions Hospitals Humans Laboratories Maternal Exposure - adverse effects Medicine Medicine and Health Sciences Parameter estimation Parents & parenting Passive smoking Pediatrics Polymorphism, Single Nucleotide Population Pregnancy Public health Quality control Regression analysis Regression models Reproductive health Risk Factors Single nucleotide polymorphisms Single-nucleotide polymorphism Smoke Smoking Smoking - adverse effects Studies Tobacco Tobacco smoke Tobacco Smoke Pollution - adverse effects Tobacco smoking |
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| Title | Joint Testing of Genotypic and Gene-Environment Interaction Identified Novel Association for BMP4 with Non-Syndromic CL/P in an Asian Population Using Data from an International Cleft Consortium |
| URI | https://www.ncbi.nlm.nih.gov/pubmed/25303326 https://www.proquest.com/docview/1610133479 https://www.proquest.com/docview/1612292156 https://pubmed.ncbi.nlm.nih.gov/PMC4193821 https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0109038&type=printable https://doaj.org/article/b15983e156d84fbfbb240d7b0046ca3b http://dx.doi.org/10.1371/journal.pone.0109038 |
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